Cytomegalovirus fetus infection and pregnancy outcomes
Human cytomegalovirus infection impacts
With all the attention of the COVID-19 causing virus (SARS-CoV-2), we have been bumping into lots of literature related to viruses in general and one virus in particular grabbed our attention as it has been reported to be the leading cause of congenital malformations in newborns worldwide (meaning, birth defects that a child is born with). Since birth defects is an important area of interest for Merogenomics, we wanted to take a deeper focus on this virus.
The virus of interest is the human cytomegalovirus (CMV) which belongs in the herpes viruses family.
First, before we get into scary descriptions of what an infection with this virus can lead to during pregnancy, let’s take a look at a recently provided number of identified newborns with CMV infection in the US: 0.014%, or approximately 1 in 7,000 births.
So luckily, potentially quite rare. A possible issue with this figure is that testing for CMV is quite uncommon, with somewhere around 0.7% of newborns being screened, and therefore the CMV infection rate might be underdiagnosed. Other surveillance studies put the rate as high as 0.2-2.5% of newborns being CMV infected. Thus, please keep in mind that these numbers can always vary between different studies and they represent ball park figures only.
Some risk factors include maternal age younger than 20 years, fever during pregnancy, placental abruption, preeclampsia, multiple gestation, small size for gestational age, and preterm birth. In addition, studies consistently show that persons of lower socioeconomic status are more likely to be CMV infected (which could be due to differences in customs, such as breastfeeding).
In the worst case scenario, CMV infection can lead to a series of birth defects and health problems: intrauterine growth restriction, microcephaly (abnormally small head due to incomplete brain development), eye anomalies, neonatal seizures, chorioretinitis (an inflammation of the lining of the retina), jaundice, anemia, hepatosplenomegaly (swelling of liver and spleen), petechiae (round spots on the skin due to bleeding), thrombocytopenia (deficiency of platelets in the blood leading to bruising, and slow blood clotting), intellectual or learning disability, sensorineural hearing loss (the most common symptom associated with fetal CMV infection and the most common cause of non-genetic of sensorineural hearing loss), and may even cause intrauterine fetal death. Of the potential birth defects, the most feared would be the microcephaly (the condition brought to great public awareness with the Zika virus infection). Of all the newborns infected with CMV, approximately 6.5% could develop microcephaly.
However, the vast majority of infections are likely to be harmless, and it is estimated that about 80% to 90% of newborns infected with CMV will be asymptomatic and some may only develop symptoms such as hearing loss later in life. As a consequence, the majority of CMV infections in newborns are typically undiagnosed.
How does CMV spread?
First, the infection rates are insanely high. CMV persistently infects over 70% of the population worldwide with some geographical locations even indicated 100% infection rate. CMV infections appear to be the highest in South America, Africa and Asia, and the lowest in Western Europe and in the United States. For most healthy people who are infected with CMV after birth, they experience only few or no symptoms and no long-term complications, and most are unaware that they have ever been infected. However, once infected, the virus usually remains dormant within a person’s body for life.
Nevertheless, there is still a substantial number of women of reproductive age in nearly all populations that are unaffected by the virus and thus at risk of infection during pregnancy, which can put the child at risk.
The only other groups of people at serious risk from a CMV infection are those with compromised immune systems where it can cause very serious complications such as pneumonia (inflammation of the lung), hepatitis (inflammation of the liver), encephalitis (inflammation of the brain), colitis (inflammation of the inner lining of the colon), and retinitis (inflammation of the retina).
Finally, CMV infection could also be associated with cancer development, especially in the brain, breast, prostate, skin and colon. Viruses such as CMV are not oncogenic directly but might promote cancer development by inducing an environment of chronic inflammation that could advance full blown malignancy. However, that link is not yet clearly established.
Transmission occurs from person to person through bodily fluids. Day care centres are a large contributor to the spread of the virus. The virus can also be transmitted from mother to the infant during delivery from contact with genital secretions or later on through breast milk, but even these early life infections lead to no clinical illness, not even for premature babies.
Thus, the biggest risk to babies is due to infection during pregnancy.
How are pregnancies affected by CMV?
The fetus can be infected during pregnancy from either a primary infection (mother’s first time becoming infected), mother becoming reinfected, or the reactivation of the virus in already infected mother. Most of the CMV fetal infections appear to be due to maternal reinfection. A maternal immune system is suppressed during pregnancy and this contributes to enhanced chances of fetal viral infection. It is believed that the placenta becomes infected first with a subsequent infection of the fetus.
Estimates suggest that the likelihood of a primary maternal infection could result in birth defects in 5–15% of CMV infected fetuses. Secondary maternal CMV infection on the other hand is estimated to lead to birth defects in CMV infected fetuses in under 2% of the time.
Therefore prior maternal infection and CMV immunity can reduce chances of both the fetal infection and birth defects but it does not completely protect the fetus from being infected itself, and it is estimated that 60% of the CMV infected fetuses occur in mothers who already developed an immunity to CMV prior to conception.
Unfortunately, the infection, and its potential resulting damage can occur at any stage of pregnancy, although earlier gestational stages appear to result in greater impact.
The mortality rate among infants born with CMV birth defects is approximately 10–30%. Only about 10% of affected infants completely recover. The remainder of infants will have long-term complications.
In addition, 10–15% of infants infected during pregnancy could develop clinical symptoms during the first 3 years of life. It appears that most cases of hearing loss due to CMV infection are late in onset as opposed to being present at birth.
How does Merogenomics get involved?
Merogenomics is not involved in this type of fetal testing for the association of birth defects, meaning Merogenomics does not help test for viral infection induced birth defects. Merogenomics is solely involved in providing access to DNA sequencing that could be analyzed in order to determine if genetic hereditary factors were the influencing causes behind any fetal anomalies.
However, Merogenomics first and foremost is dedicated to education and we see it as an important component of public understanding of the chances and causes of birth defects, with viral infection clearly one of the contributing factors.
Diagnosis of fetal CMV infection requires the collection of the amniotic fluid and testing for the presence of the viral genetic material directly in the fluid. Due to the need for the virus to have appropriate amount of time to propagate, the testing does not take place prior to the 21st week of pregnancy.
How do we stop the CMV infection consequences?
Currently, there is no approved treatment of congenital CMV infection, and antiviral drugs are the only approach to help with improving outcomes but with no guarantee of success. Unfortunately, these drugs result in substantial toxicity and so no efficient treatment or control strategy exists for CMV infections. For asymptomatic cases, they may require regular audiological evaluation for potential signs of sensorineural hearing loss.
There is also no approved vaccine for the prevention of CMV infection although this is an ongoing area of intense research and development due to the recognized need.
Prevention of maternal and fetal infection is, at the moment, the best approach. This primarily includes practicing good personal hygiene by pregnant women (thorough hand-washing with soap and water), especially after coming into contact with any bodily fluids of a child who is in day care, which should be minimized to the greatest degree possible. This is far more complex than people might realize, as we are talking about attempting elimination of contact with a saliva of another child. Women who develop a flue-like illness during pregnancy should be tested for CMV infection. For a detailed list of measures to decrease maternal risk of CMV infection check out this Canadian Pediatric Society update on CMV infections.
The take home message is that virus infections can be a contributing factor to human diseases including those that might also materialize as a consequence of inherited mutated genetics. This might not be an obvious factor of consideration. Cytomegalovirus infection of the fetus is one such example which can lead to complications sometimes associated with other factors, including genetics. Luckily, these are rare events and potentially preventable. Thus we believe awareness of these causes is valuable to expecting mothers.
Hungry for more knowledge? Check out our other posts related to pregnancy.
We wish you awesome genomes and happy pregnancy outcomes!
This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.
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